title: Age-related changes of forkhead transcription factor FOXO1 in the liver of senescence-accelerated mouse SAMP8.
abstract: SAMP8 exhibits accelerated aging and a short lifespan. Insulin-like growth factor-1 receptor (IGF-1R)/FOXO pathway is associated with aging. Phosphorylation of IGF-1R, Akt, and FOXO1 was found to be increased during aging in the liver of SAMR1 normal aging mice. However, significant decreases in the phosphorylation of IGF-1R and Akt were observed in the liver of SAMP8 during aging compared with that in SAMR1, whereas phosphorylation of FOXO1 was markedly increased with age in SAMP8. In addition, the protein level of FOXO1 was decreased with age in SAMP8. Protein phosphatase 2A (PP2A) directly dephosphorylates FOXO1. Significant reduction of PP2A activity was observed in the liver nucleus of SAMP8. These results suggest the possibility that the increased FOXO1 phosphorylation might occur by the decreased activity of PP2A, resulting in the decrease in the protein level of FOXO1 in SAMP8. Furthermore, FOXO1 regulates longevity and the expression of antioxidant enzymes such as Mn-SOD and catalase. The expression of Mn-SOD and catalase was significantly decreased in the liver of SAMP8. Therefore, it is possible that the elevation of phosphorylated FOXO1 level with age causes a short lifespan in SAMP8.
authors.affiliation: Department of Pathophysiology, Yokohama College of Pharmacy, Yokohama 245-0066, Japan. k.tomobe@hamayaku.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tomobe
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shinozuka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kawashima
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kawashima-Ohya
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000201:enzymology / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D013482:Superoxide Dismutase; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt; D054648:Protein Phosphatase 2
keywords: Antioxidant enzyme; FOXO1; IGF-1R; Longevity; SAMP8; Senescence